Secondary immunodeficiency in patients with cancer plays an important role in the infectious complications and mortality in this group. We have recently shown than prostaglandin producing peripheral blood leukocytes are the primary cause of in vitro hyporesponsiveness to T cell mitogens in patients with Hodgkin's Disease. Accordingly, this research proposal is designed to comprehensively study prostaglandin mediated immunosuppression in patients with cancer. Patients with solid tumors, Hodgkin's Disease, non-Hodgkin's Disease lymphomas, and multiple myeloma will be investigated using in vitro assays which are designed to measure the contribution of prostaglandin mediated immunosuppression to B and T cell function. These in vitro assays consist of the following: (1) The proliferative response to phytohemagglutinin with and without indomethacin (a prostaglandin synthetase inhibitor), (2) The synthesis of IgG and IgM immunoglobulins in six day pokeweed stimulated cultures with and without methacin. (3) The sensitivity of these two assays to the suppressive effect of exogenous prostaglandin E2. The results of these assays will enable us to differentiate prostaglandin mediated immunosuppression on the basis of increased prostaglandin production by circulating leukocytes versus increased sensitivity to prostaglandins. The cellular nature of the prostaglandin producing leukocyte will be established using radioimmunoassays of prostaglandins and indirect immunofluorescence for cytoplasmic prostaglandin in association with double surface marker assays for lymphocyte surface markers and biophysical cell separation techniques. The cellular mechanisms involved in prostaglandin related immunosuppression, especially a prostaglandin induced, intermediate suppressor cell, will be established. In an effort to establish if immunosuppression mediated by peripheral prostaglandin producing leukocytes may render the host more susceptible to neoplastic development or be genetically linked, treated cancer patients and blood relatives of cancer patients will also be studied. Finally, based on encouraging preliminary results, we plan to determine if immunosuppression mediated by prostaglandin producing peripheral leukocytes in cancer patients can be reversed by the administration of a prostaglandin synthetase inhibitor, indomethacin.